The present invention relates to novel cytarabine derivatives, the preparation thereof and the use thereof for controlling diseases.
AraC (=cytarabine=4-amino-1-.beta.-D-arabinofuranosyl-2(1H)-pyrimidinone or 1-.beta.-D-arabinofuranosyl-cytosine, Merck Index 11th Edition, No. 2790) is a cytostatic agent of proven use in the chemotherapy of cancers. However, AraC rapidly undergoes deamination by the cytosine deaminase present in the body and thus becomes inactive. To achieve a therapeutic effect it must therefore be administered in high doses which are associated with unpleasant side effects for the patient.
In order to delay the rapid enzymatic deamination, the amino group of the cytosine residue has been provided with acyl protective groups (Int J. Cancer 37 (1986) 149). The cytostatic effect of the resulting N.sup.4 -acyl AraC derivatives is, however, even when they are administered in the form of liposomes, no better than that of underivatized AraC. The N.sup.4 -acylamide linkage of these AraC prodrugs is able to delay enzymatic deamination in vivo for only a short time.